POS1366 RITUXIMAB IN IgG4-RD: AN OPEN-LABEL NON-RANDOMIZED OBSERVATIONAL STUDY
Authors: J. Vikse, Ø. Midtvedt, Ø. Molberg, B. T. Svanes Fevang, Ø. Palm, T. Garen, K. B. Norheim, G. Bakland, M. Wallenius, A. M. Hoffmann-Vold
Journal: Annals of the Rheumatic Diseases (2022)

Background IgG4-related disease (IgG4-RD) is a rare, heterogenous and potentially severe disease. An open-label trial demonstrated efficacy of rituximab (RTX) in IgG4-RD [1]. Recently, four distinct phenotypes of IgG4-RD were identified [2]. There is a paucity of studies investigating RTX efficacy across these phenotypes. Objectives Investigate efficacy and safety of RTX in IgG4-RD and segregated by phenotypes. Methods This is an open-label non-randomized single center observational study. All patients with IgG4-RD (diagnosed by expert opinion) at the Oslo University Hospital treated with ≥ 1 dose of RTX with 12 months follow-up were included. Two experts (JV, ØMi) assigned patients to phenotypes. Glucocorticoid (GC) treatment was allowed. We measured disease activity by the IgG4-RD Responder Index (IgG4-RD RI) at baseline, 6 months, and 12 months. We defined a composite primary outcome consisting of two measures; (i) reduced disease activity (i.e., ≥2 points improvement in IgG4-RD RI from baseline and/or IgG4-RD RI score 0 at follow-up), and (ii) no disease flares (i.e., no ≥2 points worsening of IgG4-RD RI and no need to increase GC dose) at 6 months. Secondary outcomes were (a) reduced disease activity at months 6 or 12, (b) remission (IgG4-RD RI score 0 and GC dose ≤ 7.5 mg) at 6 or 12 months and (c) safety. Descriptive statistics were applied. Results We included 40 patients, of which 30 (75%) were male and 35 (88%) Caucasian. Mean age and disease duration at time of first RTX infusion was 58 and 3 years, respectively. Seventeen of the 40 patients (43%) received RTX as add-on therapy (following GC for &gt; 3 months), while 13 (33%) received RTX as upfront combination therapy with GC, and 10 (25%) received RTX as upfront monotherapy. All 40 patients received an infusion of 1000 mg RTX at study baseline (dose 1A at week 0) and 39 of these 40 patients (98%) received a second RTX infusion (dose 1B) at week 2. Additional infusions of 500-1000 mg RTX were administered at weeks 26 (dose 2A) and 28 (dose 2B) in 24 (60%) and 7 (18%) patients, respectively. The composite primary endpoint was met by 31/40 patients (78%). Reduced disease activity at 6 and 12 months were seen in 34 (87%) and 35 (90%) patients, respectively. Fifteen patients (38%) were in remission at 6 months, and 22 (56%) were in remission at 12 months. “Retroperitoneum and Aorta” showed lowest response rates, while “Head and Neck-Limited” had the highest rate of flares (Table 1). Mild infusion reaction occurred in 8 (20%) patients. Hypogammaglobulinemia was observed in 4 (10%). Infection requiring hospitalization occurred in 6 (15%), including one fatal infection which was the only death in the study period. Table 1. All40 (100) Pancreato-Hepato-Biliary9 (23) Retroperitoneum and Aorta 6* (15) Head and Neck-Limited 14 (35) Mikulicz and Systemic 11 (28) Baseline (n=40 ) Male, n (%) 30 (75) 8 (89) 5 (83) 8 (57) 9 (82) Caucasian (%) 35 (88) 9 (100) 6 (100) 12 (86) 8 (73) Age, years (SD) 58 (14) 63 (9) 66 (3) 49 (18) 60 (11) Disease duration, years (SD) 3 (4) 4 (3) 3 (4) 2 (2) 5 (6) 2019 ACR/EULAR classification criteria (%) 28 (70) 8 (89) 3 (50) 6 (43) 11 (100) IgG4-RD RI at diagnosis (SD) 10 (6) 10 (5) 7 (4) 7 (3) 17 (4) IgG4-RD RI at RTX 1A, (SD) 8 (6) 9 (4) 5 (4) 6 (4) 12 (7) 6 months (n=39)* IgG4-RD RI (SD) 2 (2) 3 (3) 2 (2) 1 (1) 1 (2) Primary outcome, n (%) (n=40) 31 (78) 9 (100) 3 (50) 9 (64) 10 (91) Reduced disease activity, n (%) 34 (87) 9 (100) 3 (60) 12 (86) 10 (91) Remission, n (%) 15 (38) 4 (44) 0 6 (43) 5 (46) Flare, n (%) 3 (8) 0 0 3 (21) 0 12 months (n=39)* IgG4-RD RI (SD) 1 (1) 1 (1) 0 (1) 1 (1) 1 (2) Reduced disease activity, n (%) 35 (90) 9 (100) 4 (80) 12 (86) 10 (91) Remission, n (%) 22 (56) 7 (78) 3 (60) 7 (50) 5 (45) Flare, n (%) 4 (10) 1 (11) 1 (20) 2 (14) 0 *One patient died shortly after 1A, and is not included in secondary efficacy outcomes Conclusion In our observational study, RTX appears safe and effective in IgG4-RD, with the highest response in patients with Pancreato-Hepato-Biliary phenotype. Relatively low remission rates across all phenotypes indicate an unmet need for improved treatment. References [1]Carruthers MN et al. Ann Rheum Dis. 2015;74(6):1171-1177. [2]Wallace ZS et al. Ann Rheum Dis. 2019;78(3):406-412. Disclosure of Interests Jens Vikse Speakers bureau: Novartis, Consultant of: Novartis, Jupiter Life Science Consulting, Øyvind Midtvedt: None declared, Øyvind Molberg: None declared, Bjørg Tilde Svanes Fevang: None declared, Øyvind Palm: None declared, Torhild Garen: None declared, Katrine Brække Norheim: None declared, Gunnstein Bakland: None declared, Marianne Wallenius: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp &amp; Dohme, Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp &amp; Dohme, Roche, Grant/research support from: Boehringer Ingelheim